Mutant gp70 as a source of a novel CT26 tumour antigen, GSW11

Bailey, Ian G., Reeves, Emma, Elliott, Tim and James, Edd (2009) Mutant gp70 as a source of a novel CT26 tumour antigen, GSW11. Journal of Immunology, 182 (1), [41.46].

Abstract

There is accumulating evidence that CD4+ CD25+ regulatory T cells (Treg) play an important role in anti-tumour immunity by preventing effective T cell responses to tumour antigens. Tregs have also been shown to inhibit development of organ-specific autoimmune diseases suggesting they inhibit immune responses to tissue-specific self-antigens. The depletion of Tregs prior to challenge with the murine colorectal tumour, CT26, stimulates a robust, protective T cell response which is also protective to challenge with other tumours of different histological origins, such as B cell lymphomas and a renal cell carcinoma. This cross protection has not been seen with other tumour cell lines. We have identified a CT26-derived cross-protective antigen, GSW11, which was found to be encoded within the ectotropic murine leukaemia virus (emv-1) envelope protein, gp70. This protein has previously been shown to encode CT26-specific CD8 and CD4 antigens, implicating it as a 'hot-spot' for CT26 tumour antigens. Interestingly, we have identified a truncated version of gp70 which may be responsible for generation of GSW11. Expression studies have revealed increased gp70 expression in CT26 compared to other tumour cell lines, indicating the ability to cross-protect is related to the quantity of antigen (GSW11) generated.

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